Target: KatE catalase E.C number: 1.11.1.6 NBCI: NC_000913.3 PDB ID: 1GGF Organism: Leptospira interrograns Etiologic risk group Disease Information: The bacteria that cause leptospirosis are spread through the urine of infected animals, which can get into water or soil and can survive there for weeks to months. Many different kinds of wild and domestic animals carry the bacterium. Humans can become infected through contact with urine (or other body fluids, except saliva) from infected animals, contact with water, soil, or food contaminated with the urine of infected animals.The bacteria can enter the body through skin or mucous membranes (eyes, nose, or mouth), especially if the skin is broken from a cut or scratch. Drinking contaminated water can also cause infection. Links: https://www.cdc.gov/leptospirosis/infection/index.html https://www.ncbi.nlm.nih.gov/pmc/articles/PMC88975/
Essentiality:
"A hemoprotein. A manganese protein containing MnIII in the resting state, which also belongs here, is often called pseudocatalase. The enzymes from some organisms, such as Penicillium simplicissimum, can also act as a peroxidase (EC 1.11.1.7) for which several organic substances, especially ethanol, can act as a hydrogen donor. Enzymes that exhibit both catalase and peroxidase activity belong under EC 1.11.1.21, catalase-peroxidase.". Breaks down hydrogen peroxide produced by macrophagic antibodies in host, and protects the bacteria from being digested. Essential for virulence
Links: https://enzyme.expasy.org/EC/1.11.1.6 http://www.brenda-enzymes.org/enzyme.php?ecno=1.11.1.6
Druggable target: The target is druggable.
Assayable: https://www.nature.com/articles/srep03081
"The enzyme-generated oxygen bubbles trapped by Triton X-100 were visualized as foam, whose height was estimated. A calibration plot using the defined unit of catalase activity yielded the best linear fit over a range of 20–300 units" Measures foam bubbles and plots them as a measurement of catalase activity.
Also assay kit: https://www.sigmaaldrich.com/catalog/product/sigma/cat100?lang=en®ion=US, 1 kit costs $658
Structure:
Figure 1: Crystal structure of catalase HPII from escherichia coli, from PDB (ID 1GGF)
Similarity to Human: E-Value
BLASTP Human Homolog Human NP_001743.1 11 96 82 7e-31
BLAT Drug Target TTD TTDI02035 11 93 85 1e-24
BLAT Drug Target DrugBank P77872 Formic Acid 12 93 85 1e-25
Inhibitors: azide, cyanide, sulfhydryl reagents, and alkylhydroxylamine derivatives.
2-AMINO-3-(1-HYDROPEROXY-1H-INDOL-3-YL)PROPAN-1-OL is experimental drug
Expression: Expressed in Leptospira interrogans significantly. Able to be expressed in BL21(DE3)
E.C number: 1.11.1.6
NBCI: NC_000913.3
PDB ID: 1GGF
Organism: Leptospira interrograns
Etiologic risk group
Disease Information: The bacteria that cause leptospirosis are spread through the urine of infected animals, which can get into water or soil and can survive there for weeks to months. Many different kinds of wild and domestic animals carry the bacterium. Humans can become infected through contact with urine (or other body fluids, except saliva) from infected animals, contact with water, soil, or food contaminated with the urine of infected animals.The bacteria can enter the body through skin or mucous membranes (eyes, nose, or mouth), especially if the skin is broken from a cut or scratch. Drinking contaminated water can also cause infection.
Links:
https://www.cdc.gov/leptospirosis/infection/index.html
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC88975/
Essentiality:
"A hemoprotein. A manganese protein containing MnIII in the resting state, which also belongs here, is often called pseudocatalase. The enzymes from some organisms, such as Penicillium simplicissimum, can also act as a peroxidase (EC 1.11.1.7) for which several organic substances, especially ethanol, can act as a hydrogen donor. Enzymes that exhibit both catalase and peroxidase activity belong under EC 1.11.1.21, catalase-peroxidase.". Breaks down hydrogen peroxide produced by macrophagic antibodies in host, and protects the bacteria from being digested. Essential for virulence
Links:
https://enzyme.expasy.org/EC/1.11.1.6
http://www.brenda-enzymes.org/enzyme.php?ecno=1.11.1.6
Druggable target: The target is druggable.
Assayable:
https://www.nature.com/articles/srep03081
"The enzyme-generated oxygen bubbles trapped by Triton X-100 were visualized as foam, whose height was estimated. A calibration plot using the defined unit of catalase activity yielded the best linear fit over a range of 20–300 units" Measures foam bubbles and plots them as a measurement of catalase activity.
Also assay kit:
https://www.sigmaaldrich.com/catalog/product/sigma/cat100?lang=en®ion=US, 1 kit costs $658
Structure:
Figure 1: Crystal structure of catalase HPII from escherichia coli, from PDB (ID 1GGF)
Similarity to Human: E-Value
BLASTP Human Homolog Human NP_001743.1 11 96 82 7e-31
BLAT Drug Target TTD TTDI02035 11 93 85 1e-24
BLAT Drug Target DrugBank P77872 Formic Acid 12 93 85 1e-25
Inhibitors: azide, cyanide, sulfhydryl reagents, and alkylhydroxylamine derivatives.
2-AMINO-3-(1-HYDROPEROXY-1H-INDOL-3-YL)PROPAN-1-OL is experimental drug
Expression: Expressed in Leptospira interrogans significantly. Able to be expressed in BL21(DE3)
Transmembrane bound regions: 4-5 membrane bound helices
Figure 2: TMPred output graph for HPII KatE oxidoreductase
Link: https://embnet.vital-it.ch/cgi-bin/TMPRED_form_parser
Gene available: https://www.atcc.org/Search_Results.aspx?dsNav=Ntk:PrimarySearch%7cLeptospira+interrograns%7c3%7c,Ny:True,Ro:0,N:1000552&searchTerms=Leptospira+interrograns&redir=1
Gene sequence:
atgtttatccttttctcaactgtcgctggtgaaatgggttcagcggatactgttcgcgatccacgtgggttctcagtcaagttttatactgaagagggaaattatgacattgttggaaacaacacacctattttcttcatccgtgacgcgattaagtttccagattttattcacacacaaaaacgtaacccgcag
CRYSTAL STRUCTURE OF CATALASE HPII FROM ESCHERICHIA COLI